The involvement of non-canonical Wnt signaling in early cardiomorphogenesis

• Applicant: Dr. Ina Strate
• Subject Area: Developmental Biology
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 204203343

The heart is the first functional organ being formed during embryonic development. It needs to be functional from the onset of its formation because subsequent development of the embryo depends on the circulatory system for the distribution and exchange of nutrients, oxygen and waste products. Disturbances in early cardiac morphogenesis result in congenital heart defects. In humans, heart defects are among the most common birth defects and are the leading cause of birth defect-related deaths. Congenital heart defects such as septal defects, heart valve abnormalities or a transposition of the great arteries, affect 1 out of 125 live births (www.marchofdimes.com). This stresses the importance of understanding the causes for heart malformations by gaining more knowledge about early cardiac morphogenesis. There is very little understanding about the mechanisms that drive an early process of cardiac morphogenesis, the formation of a primitive heart tube. The host lab has developed unique techniques to study early processes of heart morphogenesis which I plan to utilize to carry out experiments described in this proposal. During the course of the project proposed here, I will investigate heart tube formation in wild-type embryos using confocal microscopy in combination with cell shape measurements, high-resolution confocal time-lapse recordings and cell tracking analysis to investigate processes during heart tube formation. Zebrafish embryos defective in the non-canonical Wnt (PCP) signaling component Knypek, display disturbances in linear heart tube formation. Heart tubes in kny mutants fail to form and extent properly suggesting a possible cellular mechanism regulated by PCP signaling during early heart morphogenesis. With the imaging and genetic experiments described in this proposal I will test my hypothesis and I expect these results to contribute to a better understanding of heart morphogenesis and tube formation in general.

• DFG Programme: Research Fellowships
• International Connection: Netherlands
• Host: Dr. Jeroen Bakkers